First-day Versus Early Drain Removal Following PD: a Randomized Controlled Trial (FIDEL)

First-day Versus Early Drain Removal Following Pancreaticoduodenectomy: a Randomized Controlled Trial

Pancreatic surgery is a complex discipline with a high risk of post-operative morbidity such as pancreatic fistula (POPF) with variable impact on clinical outcome. Controversies on ID placement have emerged from both randomized and non-randomized clinical studies investigating its possible role in increasing POPF and postoperative morbidity. The optimal timing for drain removal after PD is still a subject of debate: most studies have shown that outcomes are best when ID are removed in postoperative day (POD) 3 when POPF is excluded.

AIM we aim to compare postoperative surgical outcomes after PD in patients with low/medium risk for POPF (ISGPS risk class A-B-C), who undergo POD1 drains removal versus POD3 removal.

Primary aim: 1) grade B/C POPF; 2) post-pancreatectomy hemorrhage (PPH). Secondary aims: occurrence of fluid collection, sepsis, SSI, need for reintervention, length of stay, CD>3, 90 days mortality, re-admission.

Study Design:

This is a randomized, controlled, open-label study. All patients will be randomized on POD1, using computer-generated randomization codes.

Group A: Drain removal on POD 1 (in case of POD 1 DFA< 300 U/L) Group B: Drain removal on POD 3 (in case of POD 1 DFA< 300 U/L)

Study Overview

• Status: Recruiting
• Conditions: Pancreas Fistula Abdominal Drains
• Intervention / Treatment: Behavioral: 1st day removal of abdominal drain

Detailed Description

Introduction Pancreatic surgery is a complex discipline with a high risk of post-operative morbidity such as pancreatic fistula (POPF) with variable impact on clinical outcome, fluid collection and hemorrhage. For such reason the intraoperative placement of intra-abdominal drains (ID) to early detect, mitigate, and manage post-operative complications is still considered to be a routine practice.

Controversies on ID placement have emerged from both randomized and non-randomized clinical studies investigating its possible role in increasing POPF and postoperative morbidity as well as prolonged hospital stay. According to Conlon et al the presence of drains failed to reduce either the need for interventional radiologic drainage or surgical exploration for intraabdominal sepsis and was associated with the development of more intra-abdominal abscesses, collections, or fistulas. Some authors report significantly higher postoperative abdominal complications after late removal of ID. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs, not to mention that dislocation of intra-abdominal drains is an early and frequent event after major pancreatic resection.

The optimal timing for drain removal after PD is still a subject of debate: most studies have shown that outcomes are best when ID are removed in postoperative day (POD) 3 when POPF is excluded (given a specific cut off for drain fluid amylase, DFA).

Even though many authors advocate early ID removal to prevent intra-abdominal infection or fistula, in clinical practice many surgeons may feel more comfortable to maintain IDs for a prolonged period (more than 3 days) even when criteria for POPF or other abdominal complications are not met.

In some studies correlation between drain fluid amylase (DFA) in POD1 after pancreatic resections and development of POPF has been examined, defining ideal cut-off points ranging between 5.000U/L and 90 U/l3-17-20-21 (depending on intraoperative risk stratification) that can be used to achieve the best timing for drain removal.

AIM In this non-inferiority study, we aim to compare postoperative surgical outcomes after PD in patients with low/medium risk for POPF (ISGPS risk class A-B-C), who undergo POD1 drains removal versus POD3 removal.

Primary aim: occurrence of one or more pancreas-specific complications, defined according to ISGPS as:1) grade B/C POPF; 2) post-pancreatectomy hemorrhage (PPH).

Secondary aims: occurrence of fluid collection, sepsis, SSI, need for reintervention, length of stay, CD>3, 90 days mortality, re-admission.

Patients and Methods:

Study Design:

This is a randomized, controlled, open-label study. The Study will be registered in the International Standard Randomized Controlled Trial Registry.

All patients encountering inclusion criteria will be randomized on POD1, using computer-generated randomization codes.

Group A: Drain removal on POD 1 (in case of POD 1 DFA< 300 U/L) Group B: Drain removal on POD 3 (in case of POD 1 DFA< 300 U/L)

Operative technique and drains positioning:

Experienced pancreatic surgeons will be performing a standard pancreaticoduodenectomy pylorus-preserving and a Whipple procedure if lesion infiltrates the duodenum. After resection, anastomoses will be constructed on a single jejunal loop. Management of pancreatic stump consisting in single- or double-layer, end-to-side pancreatojejunostomy (PJ) with non-absorbable interrupted sutures. Given the low risk for pancreatic fistula, no externalized trans-anastomotic stent will be placed. End-to-side hepaticojejunostomy will be performed 20 cm distally to PJ with absorbable continuous or interrupted sutures, and end-to side duodenojejunostomy with absorbable interrupted sutures. Two perianastomotic open passive penrose (Easyflow) drains are placed at the end of the procedure close to biliary anastomosis and close to PJ anastomosis15.

In conclusion, we aim, through this randomized trial, to demonstrate that POD1 drains removal after PD is not inferior to POD3 removal in low and medium risk patients and, moreover, it could prevent delayed removal-related complications, helping to guide post-operative care and improve patient outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: isabella frigerio, MD; Phone Number: 00390456449187; Email: isabella.frigerio@ospedalepederzoli.it
• Study Contact Backup: Name: giovanni butturini, MD; Phone Number: 00390456449283; Email: butturinichirurgo@gmail.com

Study Locations

• Italy
  • Verona
    • Peschiera Del Garda, Verona, Italy, 37019
      • Recruiting
      • Cdcpederzoli
      • Contact: isabella frigerio, MD; Phone Number: 00390456449187; Email: isabella.frigerio@ospedalepederzoli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients (age ≥ 18 or < 85 years) undergoing elective pancreaticoduodenectomy providing informed consent.
• Intraoperative low to moderate risk for POPF (ISGPS class A-B-C)
• POD 1 DFA < 300U/L

Exclusion Criteria:

• Age <18 or >85
• Patients with high risk of developing pancreatic fistula (ISGPS class D)
• Intraoperative positioning of external or internal pancreatic stent
• POD 1 DFA ≥300
• Sinister appearance of drain effluent (defined as dark brown to clear "spring water" fluid that looks like pancreatic juice contaminated) as mentioned in literature3-22
• Early post-pancreatectomy hemorrhage
• Intraoperative conditions different from POPF risk, requiring prolonged intrabdominal drains
• Previous bilio/pancreatic surgery
• Allergy to drain materials
• Significant coagulation disorders
• Patients unable to provide informed consent.
• Clinical suspect of another surgery-related fistula different than POPF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Drain removal on POD 1; in case of POD 1 DFA< 300 U/L	Behavioral: 1st day removal of abdominal drain; once POPF is excluded in middle-low risk pancreatic resection, abdominal drains can be removed; Other Names: 3rd day removal of abdominal drains
Active Comparator: Drain removal on POD 3; in case of POD 1 DFA< 300 U/L	Behavioral: 1st day removal of abdominal drain; once POPF is excluded in middle-low risk pancreatic resection, abdominal drains can be removed; Other Names: 3rd day removal of abdominal drains

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurrence of one or more pancreas-specific complications	complications are defined according to ISGPS as:1) grade B/C POPF; 2) post-pancreatectomy hemorrhage (PPH).	up to 90 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurrence of general post operative complications	occurrence of fluid collection, sepsis, SSI, need for reintervention, length of stay, CD>3, 90 days mortality, re-admission	up to 90 days after surgery

Collaborators and Investigators

• Sponsor: Casa di Cura Dott. Pederzoli
• Collaborators: University of Padova
• Investigators: Principal Investigator: isabella frigerio, MD, Casa di Cura Dott. Pederzoli

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: pancreatic fistula pancreaticoduodenectomy drain fluid amylase
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Fistula
• Other Study ID Numbers: Cdcpederzoli

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: after interim analysis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No